Resting tachycardia, a warning sign in anorexia nervosa: case report

Background

Among psychiatric disorders, anorexia nervosa has the highest mortality rate. During an exacerbation of this illness, patients frequently present with nonspecific symptoms. Upon hospitalization, anorexia nervosa patients are often markedly bradycardic, which may be an adaptive response to progressive weight loss and negative energy balance. When anorexia nervosa patients manifest tachycardia, even heart rates in the 80–90 bpm range, a supervening acute illness should be suspected.

Case presentation

A 52-year old woman with longstanding anorexia nervosa was hospitalized due to progressive leg pain, weakness, and fatigue accompanied by marked weight loss. On physical examination she was cachectic but in no apparent distress. She had fine lanugo-type hair over her face and arms with an erythematous rash noted on her palms and left lower extremity. Her blood pressure was 96/50 mm Hg and resting heart rate was 106 bpm though she appeared euvolemic. Laboratory tests revealed anemia, mild leukocytosis, and hypoalbuminemia. She was initially treated with enteral feedings for an exacerbation of anorexia nervosa, but increasing leukocytosis without fever and worsening left leg pain prompted the diagnosis of an indolent left lower extremity cellulitis. With antibiotic therapy her heart rate decreased to 45 bpm despite minimal restoration of body weight.

Conclusions

Bradycardia is a characteristic feature of anorexia nervosa particularly with significant weight loss. When anorexia nervosa patients present with nonspecific symptoms, resting tachycardia should prompt a search for potentially life-threatening conditions.     

The Endocrinopathies of Anorexia Nervosa

ObjectiveTo describe the hormonal adaptations and alterations in anorexia nervosa.MethodsWe performed a PubMed search of the English-language literature related to the pathophysiology of the endocrine disorders observed in anorexia nervosa, and we describe a case to illustrate these findings.ResultsAnorexia nervosa is a devastating disease with a variety of endocrine manifestations. The effects of starvation are extensive and negatively affect the pituitary gland, thyroid gland, adrenal glands, gonads, and bones. Appetite is modulated by the neuroendocrine system, and characteristic patterns of leptin and ghrelin concentrations have been observed in anorexia nervosa. A thorough understanding of refeeding syndrome is imperative to nutrition rehabilitation in these patients to avoid devastating consequences. Although most endocrinopathies associated with anorexia nervosa reverse with recovery, short stature, osteoporosis, and infertility may be long-lasting complications. We describe a 20-year-old woman who presented with end-stage anorexia nervosa whose clinical course reflects the numerous complications caused by this disease.ConclusionsThe effects of severe malnutrition and subsequent refeeding are extensive in anorexia nervosa. Nutrition rehabilitation is the most appropriate treatment for these patients; however, it must be done cautiously. (Endocr Pract. 2008;14:1055-1063)     

Classification of feeding and eating disorders: review of evidence and proposals for ICD-11

Current classification of eating disorders is failing to classify most clinical presentations; ignores continuities between child, adolescent and adult manifestations; and requires frequent changes of diagnosis to accommodate the natural course of these disorders. The classification is divorced from clinical practice, and investigators of clinical trials have felt compelled to introduce unsystematic modifications. Classification of feeding and eating disorders in ICD-11 requires substantial changes to remediate the shortcomings. We review evidence on the developmental and cross-cultural differences and continuities, course and distinctive features of feeding and eating disorders. We make the following recommendations: a) feeding and eating disorders should be merged into a single grouping with categories applicable across age groups; b) the category of anorexia nervosa should be broadened through dropping the requirement for amenorrhoea, extending the weight criterion to any significant underweight, and extending the cognitive criterion to include developmentally and culturally relevant presentations; c) a severity qualifier "with dangerously low body weight" should distinguish the severe cases of anorexia nervosa that carry the riskiest prognosis; d) bulimia nervosa should be extended to include subjective binge eating; e) binge eating disorder should be included as a specific category defined by subjective or objective binge eating in the absence of regular compensatory behaviour; f) combined eating disorder should classify subjects who sequentially or concurrently fulfil criteria for both anorexia and bulimia nervosa; g) avoidant/restrictive food intake disorder should classify restricted food intake in children or adults that is not accompanied by body weight and shape related psychopathology; h) a uniform minimum duration criterion of four weeks should apply.     

Two cases of anorexia nervosa associated with Graves' disease

In this report on two cases of anorexia nervosa associated with Graves' disease, metabolism and the relationship between the two illness are considered. Case 1 was a 25-year-old female. Anorexia was associated with a stressful life situation following marriage. One year after the onset of anorexia, her condition was diagnosed as Graves' disease. In spite of high levels of serum thyroid hormone, she did not show the clinical signs and symptoms of hyperthyroidism. The hypermetabolic state of Graves' disease seems to be suppressed by the hypometabolism of anorexia. Case 2 was a 17-year-old female whose body weight, due to anorexia, at one time had decreased from 55 kg to 35.2 kg. A rebound from anorexia to bulimia increased her body weight to 80 kg in spite of an association with the hypermetabolic state of Graves' disease. In light of the abovementioned cases, it seems that the clinical picture of Graves' disease is usually hidden by the clinical symptoms of anorexia nervosa.     

Anorexia nervosa,amenorrhea, and adaptation

Female mammals under stress or in poor physical condition often delay puberty or otherwise suppress reproduction. This capacity is adaptive because it enables females to avoid reproduction when environmental conditions are not conducive to the survival of offspring. Because amenorrhea is one of the key diagnostic criteria for this condition, anorexia nervosa is discussed in an evolutionary context. It is suggested that anorexia nervosa may delay puberty in girls who are disposed to early maturity. Since there is some evidence that early and late maturers have different life histories in modern societies, the reproductive delay associated with anorexia nervosa exhibits features compatible with an evolved reproductive strategy. Insofar as anorexia nervosa is a modern phenomenon, it is unlikely that the syndrome per se is the result of selection. Rather, anorexia nervosa appears to be a reflection of the female ability to alter maturation rates and reproductive function in response to environmental conditions.     

A child with anorexia nervosa presenting with severe infection with cytopenia and hemophagocytosis: a case report

Background

Patients with anorexia nervosa in the acute phase have physical complications, such as infectious disease. Although hemophagocytic syndrome due to infection is a rare complication in anorexia nervosa, early identification for hemophagocytosis is important for avoiding a life-threatening condition.

Case presentation

We report a case of a 12-year-old girl with anorexia nervosa presenting with infection with cytopenia and hemophagocytosis during initial nutritional therapy. She developed pyrexia, abdominal pain, and diarrhea during inpatient treatment. Although intravenous antibiotics were administered, the symptoms persisted. Acinetobacter baumannii was detected in blood culture. Hemophagocytosis was present in the bone marrow. Gamma globulin therapy was effective, with improvement in symptoms and cytopenia.

Conclusions

Although our case did not fulfill the criteria of hemophagocytic syndrome, clinicians should consider severe infection in anorexia nervosa with cytopenia and hemophagocytosis.

     

Serum leptin levels in patients with anorexia nervosa before and after partial refeeding, relationships to serum lipids and biochemical nutritional parameters.

Leptin is a protein hormone produced by adipocytes that provide information about the body fat content. It was previously reported that serum leptin levels were decreased in patients with anorexia nervosa in comparison with healthy control subjects. The aim of our study was to compare serum leptin levels in patients with anorexia nervosa (n=11, initial mean BMI=15.4 kg/m2) before and after partial recovery with control age-matched subjects (n=11, mean BMI= 20.3 kg/m2) and to study the relationships of leptin levels, serum lipids and biochemical nutritional parameters. We found that serum leptin concentrations in patients with anorexia nervosa were significantly reduced in comparison with control subjects (3.61 vs 9.37 ng.ml(-1), p<0.01). Serum cholesterol, triglycerides, total protein and albumin in patients with anorexia nervosa either before or after partial recovery did not differ from the control group. After partial recovery, a significant increase in serum leptin was observed (4.83 vs 3.61 ng.ml(-1), p<0.05), but the values still remained significantly lower than in the control group (p<0.01) Leptin levels correlated positively with the body mass index in the control group and anorexia nervosa group before recovery. The correlation with BMI in the anorexia nervosa group after refeeding was not significant. No significant correlation was found between leptin concentrations and serum lipids, total protein, albumin and prealbumin, respectively. Serum leptin thus represents a sensitive parameter that reflects the nutritional status in patients with anorexia nervosa suitable for long-term follow up during refeeding therapy.     

Plasma adiponectin levels in women with anorexia nervosa.

Adiponectin is a plasma protein exclusively secreted by adipose tissue, which plays a role in modulating lipid and glucose metabolism. The plasma adiponectin concentration shows an inverse correlation with the body mass index in normal and obese individuals, but it has not been investigated in subjects with an extremely low body weight and undernutrition such as anorexia nervosa patients. We investigated plasma adiponectin levels in 21 females with anorexia nervosa. Nineteen healthy females served as the lean control group. The subjects with anorexia nervosa had a significantly lower weight and showed a tendency towards higher adiponectin levels than the control group. No correlation between adiponectin and BMI was found in patients with anorexia nervosa, while a linear negative correlation was seen in lean controls. The patient who showed the lowest adiponectin level reached a life-threatening state and required intravenous feeding in hospital. In association with improved nutrition and weight gain, the adiponectin level increased gradually until the body mass index was about 16 and then decreased subsequently as would be expected in lean normal subjects. These observations suggest that adipose tissue secretes less adiponectin and the adiponectin levels do not show an inverse correlation simply with body mass index in some subjects with severe undernutrition.     

Human pancreatic polypeptide responsiveness to insulin-induced hypoglycemia in anorexia nervosa

Patients with anorexia nervosa occasionally suffer from hypoglycemic comas. We investigated the role of human pancreatic polypeptide (HPP) in insulin-induced hypoglycemia (0.1 U/kg of regular insulin). Ten female patients with anorexia nervosa (20.7 +/- 2.0 years, mean +/- SEM; 34.9 +/- 1.7 kg, mean +/- SEM) and 8 age-matched female controls (20.9 +/- 0.6 years, 51.5 +/- 0.8 kg) were tested. In the patients with anorexia nervosa, testing was performed before and after the restoration of body weight (45.0 +/- 0.8 kg). There was no significant difference in glucose nadir between patients with anorexia nervosa and the control subjects. However, glucose recovery from nadir was delayed in patients with anorexia nervosa. In anorexia nervosa patients, the plasma pancreatic glucagon responses to insulin-induced hypoglycemia did not differ from those of the controls. Results also showed, however, that HPP responses to insulin-induced hypoglycemia were significantly higher in patients with anorexia nervosa than in controls (p less than 0.01). The increased HPP responses were still present after the restoration of body weight in anorexia nervosa patients. A complete body weight recovery or a longer period of time may be required to normalize the HPP response to insulin-induced hypoglycemia in patients with anorexia nervosa, after the restoration of body weight.     

Muscle dysmorphia: a critical review of the proposed criteria

While body-image related disorders such as anorexia nervosa have focused on thinness, only recently have clinical criteria for a disorder that centers around muscularity--muscle dysmorphia--been proposed. An individual affected by muscle dysmorphia is overly concerned with his or her degree of muscularity.This preoccupation is manifested in the individual's behavior (excessive weight lifting, excessive attention to diet, social impairment).This article examines the historical aspects and proposed criteria for muscle dysmorphia and contrasts them with those of anorexia nervosa. While the authors of the proposed criteria have suggested that muscle dysmorphia be classified as a subcategory of body dysmorphic disorder, both the historical and clinical aspects of this syndrome are more consistent with its classification as an obsessive-compulsive disorder.     

Prolonged suppression of gonadotropin secretion after weight recovery in an anorectic patient with Turner's syndrome: reduced gonadal function in anorexia nervosa is independent in part on nutrition

Two hypotheses have been postulated as to the pathogenesis of hypogonadotropinemia in anorexia nervosa; one is starvation and weight loss and the other is a psychological factor to influence gonadotropin secretion. Our patient suffered from very rare concurrence of Turner's syndrome and anorexia nervosa and a study of this experiment in nature provided important evidences concerning decreased secretion of gonadotropins in the eating disorder. The patient was diagnosed as Turner's syndrome when she was 6 years old. Her gonadotropin levels were elevated to the castrated ranges (LH 61.8 IU/l; FSH 175.8 IU/l) after 8 years of age. She was noticed to be anorectic at the age of 13 years. Serum levels of the pituitary gonadotropins were lowered (LH 2.9 IU/l; FSH 3.0 IU/l) and their responses to luteinizing hormone-releasing hormone were decreased beneath the normal prepubertal limits. After one year of the anorectic period, she recovered the weight though her gonadotropin levels remained in the very low ranges (LH 2.7 IU/l; FSH 2.5 IU/l). The results suggest that hypogonadism in anorexia nervosa is not solely caused by nutritional deficiency but rather by other factors such as psychological abnormalities.     

Cancer Incidence among Patients with Anorexia Nervosa from Sweden,Denmark and Finland

A diet with restricted energy content reduces the occurrence of cancer in animal experiments. It is not known if the underlying mechanism also exists in human beings. To determine whether cancer incidence is reduced among patients with anorexia nervosa who tend to have a low intake of energy, we carried out a retrospective cohort study of 22 654 women and 1678 men diagnosed with anorexia nervosa at ages 10-50 years during 1968-2010 according to National Hospital Registers in Sweden, Denmark and Finland. The comparison group consisted of randomly selected persons from population registers who were similar to the anorexia nervosa patients in respect to sex, year of birth and place of residence. Patients and population comparisons were followed for cancer by linkage to Cancer Registries. Incidence rate ratios (IRR) were estimated using Poisson models. In total, 366 cases of cancer (excluding non-melanoma skin cancer) were seen among women with anorexia nervosa, and the IRR for all cancer sites was 0.97 (95% CI = 0.87-1.08) adjusted for age, parity and age at first child. There were 76 breast cancers corresponding to an adjusted IRR of 0.61 (95% CI = 0.49-0.77). Significantly increased IRRs were observed for esophageal, lung, and liver cancer. Among men with anorexia nervosa, there were 23 cases of cancer (age-adjusted IRR = 1.08; 95% CI = 0.71-1.66). There seems to be no general reduction in cancer occurrence among patients with anorexia nervosa, giving little support to the energy restriction hypothesis.     

Anorexia nervosa and refusal of naso-gastric treatment: a response to Heather Draper

Imposing artificial feeding on people with anorexia nervosa may be unethical. This seems to be Heather Draper's suggestion in her article, 'Anorexia Nervosa and Respecting a Refusal of Life-Prolonging Therapy: A Limited Justification.' Although this is an important point, I shall show that the arguments supporting this point are flawed. Draper should have made a brave claim: she should have claimed that people with anorexia nervosa, who competently decide not to be artificially fed, should be respected because everybody is entitled to exercise their autonomy, not only 'in the middle' of their life, but also at the end of it, or when their own life is at stake, because autonomy also extends to the most difficult moments of our life, and, ultimately, 'stretches [.*T*.*T*.] far out into the distance' at the end of it. I explain why Draper should have made the brave claim, and why she has not made it. I conclude that a defence of people's entitlement to competently refuse artificial feeding cannot rest upon the arguments developed by Draper. Whether or not we should respect competent refusal of artificial feeding depends on the normative strength that we are ready to ascribe to the principle of autonomy, to the moral relevance that we ascribe to the circumstances in which a person's autonomy is exercised, and, perhaps, eventually, on our sense of compassion.     

Comparison of DXA and CT in the Assessment of Body Composition in Premenopausal Women With Obesity and Anorexia Nervosa

Accurate methods for assessing body composition in subjects with obesity and anorexia nervosa (AN) are important for determination of metabolic and cardiovascular risk factors and to monitor therapeutic interventions. The purpose of our study was to assess the accuracy of dual‐energy X‐ray absorptiometry (DXA) for measuring abdominal and thigh fat, and thigh muscle mass in premenopausal women with obesity, AN, and normal weight compared to computed tomography (CT). In addition, we wanted to assess the impact of hydration on DXA‐derived measures of body composition by using bioelectrical impedance analysis (BIA). We studied a total of 91 premenopausal women (34 obese, 39 with AN, and 18 lean controls). Our results demonstrate strong correlations between DXA‐ and CT‐derived body composition measurements in AN, obese, and lean controls (r = 0.77–0.95, P < 0.0001). After controlling for total body water (TBW), the correlation coefficients were comparable. DXA trunk fat correlated with CT visceral fat (r = 0.51–0.70, P < 0.0001). DXA underestimated trunk and thigh fat and overestimated thigh muscle mass and this error increased with increasing weight. Our study showed that DXA is a useful method for assessing body composition in premenopausal women within the phenotypic spectrum ranging from obesity to AN. However, it is important to recognize that DXA may not accurately assess body composition in markedly obese women. The level of hydration does not significantly affect most DXA body composition measurements, with the exceptions of thigh fat.     

Somatic comorbidity in anorexia nervosa: First results of a 21-year follow-up study on female inpatients

Background  

Anorexia nervosa is a severe psychosomatic disease with somatic complications in the long-term course and a high mortality rate. Somatic comorbidities independent of anorexia nervosa have rarely been studied, but pose a challenge to clinical practitioners. We investigated somatic comorbidities in an inpatient cohort and compared somatically ill anorexic patients and patients without a somatic comorbidity. In order to evaluate the impact of somatic comorbidity for the long-term course of anorexia nervosa, we monitored survival in a long-term follow-up.     

Long-Term Physiological Alterations and Recovery in a Mouse Model of Separation Associated with Time-Restricted Feeding: A Tool to Study Anorexia Nervosa Related Consequences

Background

Anorexia nervosa is a primary psychiatric disorder, with non-negligible rates of mortality and morbidity. Some of the related alterations could participate in a vicious cycle limiting the recovery. Animal models mimicking various physiological alterations related to anorexia nervosa are necessary to provide better strategies of treatment.

Aim

To explore physiological alterations and recovery in a long-term mouse model mimicking numerous consequences of severe anorexia nervosa.

Methods

C57Bl/6 female mice were submitted to a separation-based anorexia protocol combining separation and time-restricted feeding for 10 weeks. Thereafter, mice were housed in standard conditions for 10 weeks. Body weight, food intake, body composition, plasma levels of leptin, adiponectin, IGF-1, blood levels of GH, reproductive function and glucose tolerance were followed. Gene expression of several markers of lipid and energy metabolism was assayed in adipose tissues.

Results

Mimicking what is observed in anorexia nervosa patients, and despite a food intake close to that of control mice, separation-based anorexia mice displayed marked alterations in body weight, fat mass, lean mass, bone mass acquisition, reproductive function, GH/IGF-1 axis, and leptinemia. mRNA levels of markers of lipogenesis, lipolysis, and the brown-like adipocyte lineage in subcutaneous adipose tissue were also changed. All these alterations were corrected during the recovery phase, except for the hypoleptinemia that persisted despite the full recovery of fat mass.

Conclusion

This study strongly supports the separation-based anorexia protocol as a valuable model of long-term negative energy balance state that closely mimics various symptoms observed in anorexia nervosa, including metabolic adaptations. Interestingly, during a recovery phase, mice showed a high capacity to normalize these parameters with the exception of plasma leptin levels. It will be interesting therefore to explore further the central and peripheral effects of the uncorrected hypoleptinemia during recovery from separation-based anorexia.     

Association of CNR1 and FAAH endocannabinoid gene polymorphisms with anorexia nervosa and bulimia nervosa: evidence for synergistic effects

Endocannabinoids modulate eating behavior; hence, endocannabinoid genes may contribute to the biological vulnerability to eating disorders. The rs1049353 (1359 G/A) single nucleotide polymorphism (SNP) of the gene coding the endocannabinoid CB1 receptor ( CNR1 ) and the rs324420 (cDNA 385C to A) SNP of the gene coding fatty acid amide hydrolase (FAAH), the major degrading enzyme of endocannabinoids, have been suggested to have functional effects on mature proteins. Therefore, we explored the possibility that those SNPs were associated to anorexia nervosa and/or bulimia nervosa. The distributions of the CNR1 1359 G/A SNP and of the FAAH cDNA 385C to A SNP were investigated in 134 patients with anorexia nervosa, 180 patients with bulimia nervosa and 148 normal weight healthy controls. Additive effects of the two SNPs in the genetic susceptibility to anorexia nervosa and bulimia nervosa were also tested. As compared to healthy controls, anorexic and bulimic patients showed significantly higher frequencies of the AG genotype and the A allele of the CNR1 1359 G/A SNP. Similarly, the AC genotype and the A allele of the FAAH cDNA 385C to A SNP were significantly more frequent in anorexic and bulimic individuals. A synergistic effect of the two SNPs was evident in anorexia nervosa but not in bulimia nervosa. Present findings show for the first time that the CNR1 1359 G/A SNP and the FAAH cDNA 385C to A SNP are significantly associated to anorexia nervosa and bulimia nervosa, and demonstrate a synergistic effect of the two SNPs in anorexia nervosa.     

Atypical responses to morphine in mice: a possible relationship to anorexia nervosa?

According to our previously proposed auto-addiction hypothesis of chronic anorexia nervosa, patients become addicted to an initial period of dieting through endogenous opioid mediated mechanisms. Morphine causes hyperactivity and anorexia in the mouse, symptoms of anorexia nervosa but responses opposite to those of most species including rats and normal human subjects. This suggests that the atypical opioid systems in the mouse may resemble those of the chronic anorexia nervosa patient in contrast to those of most species including the normal human. Characterization of this atypical opioid system may be useful in understanding the pathophysiology of anorexia nervosa.     

Hypothalamic pituitary adrenal function in patients with anorexia nervosa.

Hypothalamic pituitary adrenal function was studied in 14 patients with anorexia nervosa. Although basal plasma cortisol levels in the morning were elevated in most cases, basal plasma ACTH levels were not suppressed. Oral administration of 1 mg dexamethasone 10 hr before blood sampling failed to suppress plasma ACTH and cortisol levels in most patients with anorexia nervosa. Apparent biological half-life of exogenous cortisol was prolonged in all 4 patients with anorexia nervosa tested. The cortisol response to insulin-induced hypoglycemia and exogenous ACTH appeared to be blunted in these patients. It is concluded that anorexia nervosa has dysfunctions of hypothalamic pituitary adrenal axis, especially an abnormal feedback mechanism on ACTH secretion.     

Relation between Aspects of Nutritional Disturbance and Menstrual Activity in Primary Anorexia Nervosa

A significantly high number of patients with anorexia nervosa are overweight immediately before the onset of the condition. This premorbid weight may be a feature of their constitution but is sometimes a more transitory phenomenon. Menstruation ceases early in the condition but usually within the context of significant weight loss. However, the subsequent amenorrhoea, related to factors that presumably may not begin to operate until several weeks later, may be a symptom which first draws attention to the condition.Treatment included the restitution of body weight to the matched population mean weight for each patient. This may be important, as the mean weight at which menstrual activity returned was not significantly different from the matched population mean weight. A further treatment aim, so far as nutrition was concerned. was restoration of regular and reasonable feeding behaviour, including adequate carbohydrate ingestion. It is suggested that these findings support the view that the nutritional disturbance in anorexia nervosa is an important factor affecting menstrual activity.